{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:20:41Z","timestamp":1790162441750,"version":"4.1.0"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,11,17]]},"abstract":"<jats:p>\n                    Several species of African trypanosomes cause fatal disease in livestock, but most cannot infect humans due to innate trypanosome lytic factors (TLFs). Human TLFs are pore forming high-density lipoprotein (HDL) particles that contain apolipoprotein L-I (apoL-I) the trypanolytic component, and haptoglobin-related protein (Hpr), which binds free hemoglobin (Hb) in blood and facilitates the uptake of TLF via a trypanosome haptoglobin-hemoglobin receptor. The human-infective\n                    <jats:italic>Trypanosoma brucei rhodesiense<\/jats:italic>\n                    escapes lysis by TLF by expression of serum resistance-associated (SRA) protein, which binds and neutralizes apoL-I. Unlike humans, baboons are not susceptible to infection by\n                    <jats:italic>T. b. rhodesiense<\/jats:italic>\n                    due to previously unidentified serum factors. Here, we show that baboons have a TLF complex that contains orthologs of Hpr and apoL-I and that full-length baboon apoL-I confers trypanolytic activity to mice and when expressed together with baboon Hpr and human apoA-I, provides protection against both animal infective and the human-infective\n                    <jats:italic>T. brucei rhodesiense<\/jats:italic>\n                    in vivo. We further define two critical lysines near the C terminus of baboon apoL-1 that are necessary and sufficient to prevent binding to SRA and thereby confer resistance to human-infective trypanosomes. These findings form the basis for the creation of TLF transgenic livestock that would be resistant to animal and human-infective trypanosomes, which would result in the reduction of disease and the zoonotic transmission of human infective trypanosomes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0905669106","type":"journal-article","created":{"date-parts":[[2009,10,26]],"date-time":"2009-10-26T21:47:49Z","timestamp":1256593669000},"page":"19509-19514","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":62,"title":["Hydrodynamic gene delivery of baboon trypanosome lytic factor eliminates both animal and human-infective African trypanosomes"],"prefix":"10.1073","volume":"106","author":[{"given":"Russell","family":"Thomson","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology, New York University Langone School of Medicine, 341, East 25th Street, New York, NY, 10010; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Molina-Portela","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, New York University Langone School of Medicine, 341, East 25th Street, New York, NY, 10010; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Mott","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Carrington","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayne","family":"Raper","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, New York University Langone School of Medicine, 341, East 25th Street, New York, NY, 10010; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,11,17]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0020-7519(01)00146-1","article-title":"Some general aspects of the distribution and epidemiology of bovine trypanosomosis in southern africa","volume":"31","author":"Van den Bossche P","year":"2001","unstructured":"P Van den Bossche, Some general aspects of the distribution and epidemiology of bovine trypanosomosis in southern africa. Int J Parasitol 31, 592\u2013598 (2001).","journal-title":"Int J Parasitol"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0065-308X(05)61005-6","article-title":"Human African trypanosomiasis: Epidemiology and control","volume":"6","author":"Fevre EM","year":"2006","unstructured":"EM Fevre, K Picozzi, J Jannin, SC Welburn, I Maudlin, Human African trypanosomiasis: Epidemiology and control. Adv In Parasitol 6, 167\u2013222 (2006).","journal-title":"Adv In Parasitol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molbiopara.2004.07.004","article-title":"Characterization of primate trypanosome lytic factors","volume":"138","author":"Lugli EB","year":"2004","unstructured":"EB Lugli, M Pouliot, P Portela Mdel, MR Loomis, J Raper, Characterization of primate trypanosome lytic factors. Mol Biochem Parasitol 138, 9\u201320 (2004).","journal-title":"Mol Biochem Parasitol"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/j.1550-7408.1990.tb01163.x","article-title":"A survey for a trypanocidal factor in primate sera","volume":"37","author":"Seed JR","year":"1990","unstructured":"JR Seed, JB Sechelski, MR Loomis, A survey for a trypanocidal factor in primate sera. J Protozool 37, 393\u2013400 (1990).","journal-title":"J Protozool"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nrmicro1428","article-title":"The trypanolytic factor of human serum","volume":"4","author":"Pays E","year":"2006","unstructured":"E Pays, et al., The trypanolytic factor of human serum. Nat Rev Microbiol 4, 477\u2013486 (2006).","journal-title":"Nat Rev Microbiol"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1128\/IAI.67.4.1910-1916.1999","article-title":"Characterization of a novel trypanosome lytic factor from human serum","volume":"67","author":"Raper J","year":"1999","unstructured":"J Raper, R Fung, J Ghiso, V Nussenzweig, S Tomlinson, Characterization of a novel trypanosome lytic factor from human serum. Infect Immun 67, 1910\u20131916 (1999).","journal-title":"Infect Immun"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nature01461","article-title":"Apolipoprotein L-I is the trypanosome lytic factor of human serum","volume":"422","author":"Vanhamme L","year":"2003","unstructured":"L Vanhamme, et al., Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature 422, 83\u201387 (2003).","journal-title":"Nature"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1182\/blood-2006-05-022327","article-title":"Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein","volume":"108","author":"Nielsen MJ","year":"2006","unstructured":"MJ Nielsen, et al., Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma protein. Blood 108, 2846\u20132849 (2006).","journal-title":"Blood"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.molbiopara.2005.08.018","article-title":"Trypanosome lytic factor, a subclass of high-density lipoprotein, forms cation-selective pores in membranes","volume":"144","author":"Molina-Portela Mdel P","year":"2005","unstructured":"P Molina-Portela Mdel, EB Lugli, E Recio-Pinto, J Raper, Trypanosome lytic factor, a subclass of high-density lipoprotein, forms cation-selective pores in membranes. Mol Biochem Parasitol 144, 218\u2013226 (2005).","journal-title":"Mol Biochem Parasitol"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1126\/science.1114566","article-title":"Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes","volume":"309","author":"Perez-Morga D","year":"2005","unstructured":"D Perez-Morga, et al., Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes. Science 309, 469\u2013472 (2005).","journal-title":"Science"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"32578","DOI":"10.1074\/jbc.M503510200","article-title":"Human high density lipoproteins are platforms for the assembly of multi-component innate immune complexes","volume":"280","author":"Shiflett AM","year":"2005","unstructured":"AM Shiflett, JR Bishop, A Pahwa, SL Hajduk, Human high density lipoproteins are platforms for the assembly of multi-component innate immune complexes. J Biol Chem 280, 32578\u201332585 (2005).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1084\/jem.20071463","article-title":"Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model","volume":"205","author":"Molina-Portela MP","year":"2008","unstructured":"MP Molina-Portela, M Samanovic, J Raper, Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model. J Exp Med 205, 1721\u20131728 (2008).","journal-title":"J Exp Med"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0166-6851(01)00420-0","article-title":"No trypanosome lytic activity in the sera of mice producing human haptoglobin-related protein","volume":"119","author":"Hatada S","year":"2002","unstructured":"S Hatada, et al., No trypanosome lytic activity in the sera of mice producing human haptoglobin-related protein. Mol Biochem Parasitol 119, 291\u2013294 (2002).","journal-title":"Mol Biochem Parasitol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1126\/science.1156296","article-title":"A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans","volume":"320","author":"Vanhollebeke B","year":"2008","unstructured":"B Vanhollebeke, et al., A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans. Science 320, 677\u2013681 (2008).","journal-title":"Science"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"e129","DOI":"10.1371\/journal.ppat.0030129","article-title":"Hemoglobin is a co-factor of human trypanosome lytic factor","volume":"3","author":"Widener J","year":"2007","unstructured":"J Widener, et al., Hemoglobin is a co-factor of human trypanosome lytic factor. PLoS Pathog 3, e129 (2007).","journal-title":"PLoS Pathog"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1128\/EC.5.1.132-139.2006","article-title":"Serum resistance-associated protein blocks lysosomal targeting of trypanosome lytic factor in Trypanosoma brucei","volume":"5","author":"Oli MW","year":"2006","unstructured":"MW Oli, LF Cotlin, AM Shiflett, SL Hajduk, Serum resistance-associated protein blocks lysosomal targeting of trypanosome lytic factor in Trypanosoma brucei. Eukaryot Cell 5, 132\u2013139 (2006).","journal-title":"Eukaryot Cell"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.molbiopara.2003.11.006","article-title":"Distribution of apolipoprotein L-I and trypanosome lytic activity among primate sera","volume":"134","author":"Poelvoorde P","year":"2004","unstructured":"P Poelvoorde, L Vanhamme, J Van Den Abbeele, WM Switzer, E Pays, Distribution of apolipoprotein L-I and trypanosome lytic activity among primate sera. Mol Biochem Parasitol 134, 155\u2013157 (2004).","journal-title":"Mol Biochem Parasitol"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0166-6851(95)00019-W","article-title":"High-density-lipoprotein-independent killing of Trypanosoma brucei by human serum","volume":"70","author":"Tomlinson S","year":"1995","unstructured":"S Tomlinson, et al., High-density-lipoprotein-independent killing of Trypanosoma brucei by human serum. Mol Biochem Parasitol 70, 131\u2013138 (1995).","journal-title":"Mol Biochem Parasitol"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1365-2362.2006.01597.x","article-title":"Lipoprotein profiles in plasma and interstitial fluid analyzed with an automated gel-filtration system","volume":"36","author":"Parini P","year":"2006","unstructured":"P Parini, L Johansson, A Broijersen, B Angelin, M Rudling, Lipoprotein profiles in plasma and interstitial fluid analyzed with an automated gel-filtration system. Eur J Clin Invest 36, 98\u2013104 (2006).","journal-title":"Eur J Clin Invest"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/nm1395","article-title":"Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor","volume":"12","author":"Baral TN","year":"2006","unstructured":"TN Baral, et al., Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor. Nat Med 12, 580\u2013584 (2006).","journal-title":"Nat Med"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.cell.2007.08.046","article-title":"Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes","volume":"131","author":"Engstler M","year":"2007","unstructured":"M Engstler, et al., Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 131, 505\u2013515 (2007).","journal-title":"Cell"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1101\/gr.085647.108","article-title":"The apolipoprotein L family of programmed cell death and immunity genes rapidly evolved in primates at discrete sites of host-pathogen interactions","volume":"19","author":"Smith EE","year":"2009","unstructured":"EE Smith, HS Malik, The apolipoprotein L family of programmed cell death and immunity genes rapidly evolved in primates at discrete sites of host-pathogen interactions. Genome Res 19, 850\u2013858 (2009).","journal-title":"Genome Res"},{"key":"e_1_3_4_23_2","first-page":"39","article-title":"Infectivity of Trypanosoma (Trypanozoon) brucei gambiense for baboons (Papio hamadryas, Papio papio)","volume":"71","author":"Kageruka P","year":"1991","unstructured":"P Kageruka, et al., Infectivity of Trypanosoma (Trypanozoon) brucei gambiense for baboons (Papio hamadryas, Papio papio). 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J Gene Med 6, 584\u2013592 (2004).","journal-title":"J Gene Med"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/nprot.2007.132","article-title":"Gene splicing and mutagenesis by PCR-driven overlap extension","volume":"2","author":"Heckman KL","year":"2007","unstructured":"KL Heckman, LR Pease, Gene splicing and mutagenesis by PCR-driven overlap extension. Nat Protoc 2, 924\u2013932 (2007).","journal-title":"Nat Protoc"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0166-6851(03)00055-0","article-title":"Structural features affecting variant surface glycoprotein expression in Trypanosoma brucei","volume":"128","author":"Wang J","year":"2003","unstructured":"J Wang, U Bohme, GA Cross, Structural features affecting variant surface glycoprotein expression in Trypanosoma brucei. Mol Biochem Parasitol 128, 135\u2013145 (2003).","journal-title":"Mol Biochem Parasitol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0905669106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T02:40:55Z","timestamp":1654569655000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0905669106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,11,17]]},"references-count":26,"journal-issue":{"issue":"46","published-print":{"date-parts":[[2009,11,17]]}},"alternative-id":["10.1073\/pnas.0905669106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0905669106","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1167959.895054","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1167959.630060","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,17]]},"assertion":[{"value":"2009-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}